Date of Award
Union College Only
Bachelor of Science
cortisol, hypothalamic-pituitary-adrenal (HPA) axis, stress, Cushing's Syndrome, Metabolic Syndrome, single nucleotide polymorphism (SNP), bariatrics, DNA isolation, polymerase chain reaction (PCR), gel electrophoresis
The human body’s primary stress response is regulated through the secretion of the glucocorticoid hormone cortisol through the hypothalamic-pituitary-adrenal (HPA) axis. Utilizing glucocorticoid receptors (GR), cortisol regulates the expression of certain genes that play a role in metabolism regulation and obesity related conditions such as type 2 diabetes, insulin resistance, and elevated serum triglycerides. Based on this, our lab and others have identified the presence of mutations in the genes for the glucocorticoid receptor (GR), the closely related mineralocorticoid receptor (MR), and regulatory proteins associated with cortisol or GR function (heat shock protein 90, 11ß-hydroxysteroid dehydrogenase type 1, and FK506 binding protein (FKBP)) to be of higher frequency in obese populations. Our study continued to investigate the genotypic frequency of these single nucleotide polymorphisms in the clinical population of bariatric patients from Ellis Hospital in hopes to better understand the role of genotypic variation in cortisol regulation and obesity. Our study also investigated the correlation between one’s success in bariatric surgery (measured by percent excess body weight loss) and one’s genotype for each SNP. DNA samples were extracted from buccal swabs of Ellis Hospital participants and analyzed using allele specific polymerase chain reactions to determine the genotypic frequency of SNPs associated with hypersensitivity or resistance to cortisol. From the polymorphisms tested, a higher mutant allele frequency was seen in the bariatric population compared to the general population for SNPS: BclI, N363S, and rs120. A lower mutant allele frequency was seen in the bariatric population compared to the general population for SNPs: tthIII and FK506. Significant correlations could not be made between percent excess body weight loss and genotypes for each SNP due to small population size. In addition, our study designed a new multiplex assay in which wild type and mutant alleles can be tested in a single PCR reaction to greatly increase the efficiency of data collection. With a greater sample population, more significant correlations can be made between SNPs and obesity to aid in the steps towards personalized medicine based on one’s genetic information.
O'Brien, Margot, "Impact of Single Nucleotide Polymorphisms in HPA Axis Functionality in Obese Populations" (2019). Honors Theses. 2338.